DataSheet1_SIPA1 Enhances Aerobic Glycolysis Through HIF-2α Pathway to Promote Breast Cancer Metastasis.ZIP

Increased dependence on aerobic glycolysis is characteristic of most cancer cells, whereas the mechanism underlying the promotion of aerobic glycolysis in metastatic breast cancer cells under ambient oxygen has not been well understood. Here, we demonstrated that aberrant expression of signal-induced proliferation-associated 1 (SIPA1) enhanced aerobic glycolysis and altered the main source of ATP production from oxidative phosphorylation to glycolysis in breast cancer cells. We revealed that SIPA1 promoted the transcription of EPAS1, which is known as the gene encoding hypoxia-inducible factor-2α (HIF-2α) and up-regulated the expression of multiple glycolysis-related genes to increase aerobic glycolysis. We also found that blocking aerobic glycolysis by either knocking down SIPA1 expression or oxamate treatment led to the suppression of tumor metastasis of breast cancer cells both in vitro and in vivo. Taken together, aberrant expression of SIPA1 resulted in the alteration of glucose metabolism from oxidative phosphorylation to aerobic glycolysis even at ambient oxygen levels, which might aggravate the malignancy of breast cancer cells. The present findings indicate a potential target for the development of therapeutics against breast cancers with dysregulated SIPA1 expression.</p

Magnetic hybrid organic-inorganic perovskite (CH3NH3)2XCl4(X = Mn, Cu, Co) crystals

For the hybrid organic-inorganic perovskites with the general formula of A2MIIX4(A = methylammonium; MII= Mn, Cu and Co; X = Cl), the arrangement of metal ions and organic ligands leads to a delicate balance of space, spin and charge, which results in diverse properties. In this paper, we reported a group of hybrid organic-inorganic perovskite single crystals of (CH3NH3)2MnCl4, (CH3NH3)2CuCl4and (CH3NH3)2CoCl4grown by a simple solution evaporation method. Magnetic measurements show that all the single crystals display magnetic ordering at low temperature. Our results reveal a novel group of hybrid organic-inorganic magnetic perovskites

DataSheet2_SIPA1 Enhances Aerobic Glycolysis Through HIF-2α Pathway to Promote Breast Cancer Metastasis.docx

Increased dependence on aerobic glycolysis is characteristic of most cancer cells, whereas the mechanism underlying the promotion of aerobic glycolysis in metastatic breast cancer cells under ambient oxygen has not been well understood. Here, we demonstrated that aberrant expression of signal-induced proliferation-associated 1 (SIPA1) enhanced aerobic glycolysis and altered the main source of ATP production from oxidative phosphorylation to glycolysis in breast cancer cells. We revealed that SIPA1 promoted the transcription of EPAS1, which is known as the gene encoding hypoxia-inducible factor-2α (HIF-2α) and up-regulated the expression of multiple glycolysis-related genes to increase aerobic glycolysis. We also found that blocking aerobic glycolysis by either knocking down SIPA1 expression or oxamate treatment led to the suppression of tumor metastasis of breast cancer cells both in vitro and in vivo. Taken together, aberrant expression of SIPA1 resulted in the alteration of glucose metabolism from oxidative phosphorylation to aerobic glycolysis even at ambient oxygen levels, which might aggravate the malignancy of breast cancer cells. The present findings indicate a potential target for the development of therapeutics against breast cancers with dysregulated SIPA1 expression.</p

Table_1_CircGLIS3 Promotes High-Grade Glioma Invasion via Modulating Ezrin Phosphorylation.docx

High-grade glioma is highly invasive and malignant, resistant to combined therapies, and easy to relapse. A better understanding of circular RNA (circRNA) biological function in high-grade glioma might contribute to the therapeutic efficacy. Here, a circRNA merely upregulated in high-grade glioma, circGLIS3 (hsa_circ_0002874, originating from exon 2 of GLIS3), was validated by microarray and Real-time quantitative reverse transcription PCR (qRT-PCR). The role of circGLIS3 in glioma was assessed by functional experiments both in vitro and in vivo. Fluorescence in situ hybridization (FISH), RNA pull-down, RNA immunoprecipitation (RIP), and immunohistochemical staining were performed for mechanistic study. Cocultured brain endothelial cells with glioma explored the role of exosome-derived circGLIS3 in the glioma microenvironment. We found that upregulation of circGLIS3 promoted glioma cell migration and invasion and showed aggressive characteristics in tumor-bearing mice. Mechanistically, we found that circGLIS3 could promote the Ezrin T567 phosphorylation level. Moreover, circGLIS3 could be excreted by glioma through exosomes and induced endothelial cell angiogenesis. Our findings indicate that circGLIS3 is upregulated in high-grade glioma and contributes to the invasion and angiogenesis of glioma via modulating Ezrin T567 phosphorylation.</p

Supplemental Figure 1 from Clinical Trial Characteristics and Barriers to Participant Accrual: The MD Anderson Cancer Center Experience over 30 years, a Historical Foundation for Trial Improvement

Trial Inclusion Diagram</p

Supplemental Table 1-2 from Clinical Trial Characteristics and Barriers to Participant Accrual: The MD Anderson Cancer Center Experience over 30 years, a Historical Foundation for Trial Improvement

Supplemental Tables 1-2</p

Supplemental Figure Legend from Clinical Trial Characteristics and Barriers to Participant Accrual: The MD Anderson Cancer Center Experience over 30 years, a Historical Foundation for Trial Improvement

Figure legend for supplemental figures</p

Supplemental Figure 2 from Clinical Trial Characteristics and Barriers to Participant Accrual: The MD Anderson Cancer Center Experience over 30 years, a Historical Foundation for Trial Improvement

Slow accruing national cooperative group trials with respect to submission year</p

DataSheet1_Application of 3D Hepatic Plate-Like Liver Model for Statin-Induced Hepatotoxicity Evaluation.PDF

Background: Drug-induced liver injury is one of the main reasons of withdrawals of drugs in postmarketing stages. However, an experimental model(s) which can accurately recapitulates liver functions and reflects the level of drug hepatotoxicity is lack. In this study, we assessed drug hepatotoxicity using a novel three-dimensional hepatic plate-like hydrogel fiber (3D-P) co-culture system.Methods: During the 28-days culture period, the liver-specific functions, hepatocyte polarity, sensitivity of drug-induced toxicity of 3D-P co-culture system were evaluated with 2D co-culture, collagen sandwich co-culture, 3D hybrid hydrogel fiber co-culture and human primary hepatocytes as controls. High-content imaging and analysis (HCA) methods were used to explore the hepatotoxicity mechanism of five statins.Results: The 3D-P co-culture system showed enhancing liver-specific functions, cytochrome P450 enzymes (CYPs) metabolic activity and bile excretion, which were considered to result from improved hepatocyte polarity. Three of the statins may cause acute or chronic hepatotoxicity by via different mechanisms, such as cholestatic liver injury.Conclusion: Our 3D-P co-culture system is characterized by its biomimetic hepatic plate-like structure, long-term stable liver specificity, and prominent bile secretion function, making it applicable for acute/chronic drug hepatotoxicity assessments.</p